1. Field of the Invention
The present invention relates generally to milk production, and more particularly, to pharmacological agents that decrease milk production in at least humans, rodents, and domestic animals to include cattle, goats, sheep, swine and horses.
2. Description of the Related Art
The mammary gland is a complex, specialized organ which typically stays quiescent until pregnancy and post-partum period. The initiation of lactation following parturition is a dynamic processes involving homeostatic and homeorhetic changes throughout the organism. Consequently, these shifts in physiology are accompanied by changes in endocrine hormones and locally produced factors to meet the demands of the mammary gland.
Involution, that is, the cessation of lactation and regression of a mammary gland, was originally believed to be a termination of suckling-induced positive signals leading to cell death and tissue remodeling. However, it is now known that a cohort of genes and molecules are activated and involved locally in the process of involution. It is also been demonstrated that each functional unit of the mammary gland auto regulates itself independent of endocrine influences.
Rapid dry off, involution, may be crucial to the prevention of mastitis infections within mammary glands, not to mention overall health of the woman or animal. Acceleration of dry off has also been associated with increased production efficiency in dairy animals.
The rate of milk secretion by a lactating animal is regulated in part by the frequency of milk removal. Thus, there is a mechanism to match an animal's supply of milk to the demand of her offspring or of a farmer's milking regime. This mechanism is controlled partially a release of galactopoietic hormones during suckling or milking. However, research has indicated that there may also be other factors, including inhibitors which decrease milk secretion at a local level, i.e. at an individual mammary gland.
One proposed local mechanism is based on the ability of the mammary gland to store fluid within extracellular space. This mechanism is controlled and occurs within each gland and is located in the mammary alveoli in order to regulate a degree of alveolar distension over a short-term period of time, and to adjust milk secretion to demand of offspring and/or frequency of milking over a long-term period of time.
It is known in the art that serotonin, in a variety of species, is associated with decreasing milk gene expression, decreasing milk yield, and disrupting tight junctions. Furthermore, a serotonin reuptake transporter (also known as “SERT”) has been identified in the same variety of species, and a metabolite of serotonin in the form of 5-hydroxyindole acetic acid has been found in milk of the same species.
It is also known that the SERT functions to regulate the entire serotonergic system by regulating extracellular fluid concentrations of serotonin, and that serotonin may be broken down by an enzyme, monoamine oxidase (also known as “MAO”).
Based in part on the above, it has been questioned whether there is a means of manipulating an intrinsic feedback pathway regulated by serotonin such that a significantly rapid cessation of milk production in a mammary gland is witnessed.